Chronic kidney disease (CKD) is an important risk factor for
cardiovascular disease (CVD). Increased oxidative stress plays a role in the pathogenesis of CVD in CKD patients. The oral
charcoal adsorbent
AST-120 attenuates the progression of CKD possibly by removing uraemic toxins such as
indoxyl sulfate (IS), and reduces oxidative stress. We investigated the relationship between oxidative stress and cardiac damage in CKD and its prevention by
AST-120.
METHODS: Male Lewis rats were administered
adriamycin at 8 weeks of age, and the right kidney was removed at 12 weeks of age. From 14 weeks of age, the rats were treated daily with
AST-120 (n = 8) or were untreated (control group, n = 8). At 34 weeks of age, the rats were killed and urinary and blood biochemical tests as well as cardiac histological analyses were performed.
RESULTS: At 14 weeks of age, there were no significant differences in blood pressure, renal function (
creatinine clearance: 1.54 +/- 0.28 mL/min versus 1.60 +/- 0.22 mL/min), oxidative stress markers or other biochemical data between the control and
AST-120 groups. At 34 weeks, despite similar blood pressure and renal function (
creatinine clearance: 0.78 +/- 0.46 mL/min versus 0.75 +/- 0.54 mL/min), serum concentrations of IS and urinary excretion of
8-hydroxydeoxyguanosine (8-OHdG),
acrolein and IS were significantly lower in the
AST-120 group than in the control group. Heart volume, left ventricular volume and cardiac
fibrosis were significantly smaller in the experimental
AST-120 group than in the control group. Immunohistological analysis revealed that the numbers of 8-OHdG- and
acrolein-positive cardiomyocytes and the degrees of myocardial and perivascular
fibrosis were ameliorated by
AST-120 administration. The myocardial
fibrosis score was significantly associated with the 8-OHdG- (r = 0.848, P < 0.001) and
acrolein-positive (r = 0.812, P < 0.001) cell scores. The perivascular
fibrosis score was also significantly associated with the 8-OHdG- (r = 0.906, P < 0.0001) and
acrolein-positive (r = 0.789, P < 0.001) cell scores.
CONCLUSIONS: